Nicotinic acid is an oxide of nicotine and one of vitamin B complex. It is a water soluble vitamin, which is also called niacin, or vitamin B3 and prevalent in animal and plant. Deficiency of nicotinic acid may cause pellagra disease or neuropathies. In general, nicotinic acid is present in the form of nicotinic acid amide coenzyme, i.e., nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP), in vivo, and is involved in oxidation reduction reactions.
Quinolinate, which is also called quinolinic acid, is produced by oxidation of quinoline. Quinolinic acid is known to have neurotoxicity and cause various neurological disorders. Quinolinate is also known as a precursor of nicotinic acid.
Nicotinic acid that is widely applicable to the foods and medicinal products may be prepared by a chemical synthetic method or a biological production method. Chemical synthesis of nicotinic acid may result in large quantities of toxic waste including catalysts. Thus, the waste is required for a thorough management and great expenses for disposal. In addition, pyrimidine used as a precursor has various derivatives, and then fluctuations in supply and price of pyrimidine cause an unstable price of nicotinic acid.
To solve the such problems from the chemical synthesis method, biological methods of producing nicotinic acid by using renewable carbohydrate-derived materials have been studied. Biological production of nicotinic acid is accomplished mainly through two biosynthetic pathways, one of which is a biosynthetic pathway of nicotinic acid from tryptophan as a starting material in eukaryotes, and the other is from aspartic acid as a starting material as in prokaryotes. Both of the pathways use quinolinate as an intermediate, and biosynthesize nicotinic acid from quinolinate by the action of quinolinate phosphoribosyltransferase (nadC), nicotinate-mononucleotide adenyl transferase (nadD), NAD synthetase (nadE), nicotinamide-nucleotide adenyl transferase (NMN nadR), and nicotinamidase (pncA).
Biological synthesis methods of nicotinic acid by using recombinant E. coli or Corynebacterium glutamicum via the pathway of aspartic acid is disclosed (Korean Patent No. 10-1223904). While the inventors of the present invention researched to address the problems from such biological synthesis methods of nicotinic acid and to improve the yield of quinolinate or nicotinic acid, they found enzyme variants involved in the high-yield production of quinolinate and completed the present invention.